Treatment of pulmonary hypertension

• Diuretics are needed to control oedema from right heart failure and home oxygen to correct hypoxia.
  
• Anticoagulation is recommended in pulmonary arterial hypertension (PAH) and is essential for patients with chronic thromboembolic pulmnary hypertension (CTEPH).
  • Primary (idiopathic) pulmonary hypertension is treated with anticoagulants (because it is virtually impossible to rule out persistent micro-emboli as the cause).
    
• Calcium channel blockers are indicated in a small subset of patients with idiopathic hypertension who show a vasoreactive response at right heart catheterisation.
  
• In patients with group 1 pulmonary arterial hypertension (idiopathic PAH, PAH associated with connective tissue disease - predominantly seen with scleroderma) (1).
  • Specific drugs have been found to be beneficial in randomised controlled trials with improvement in symptoms, delayed disease progression and improved survival.
  • There are three main drug classes: prostanoids delivered iv, by nebuliser or subcutaneous (eg epoprostenol, iloprost, treprostinil), endothelin receptor antagonists (eg bosentan, ambrisentan), and phosphodiesterase inhibitors (eg sildenafil, tadalafil).
    • These drugs are only prescribed through the designated centres.
    • Side effects include flushing, headaches, gastro-intestinal disturbance and hypotension.
    • Endothelin receptor antagonists require monthly liver function monitoring.

CTEPH

• Treatment of choice for patients with CTEPH is pulmonary endarterectomy (PEA) surgery.
• Lifelong anticoagulation is also recommended; antiplatelet therapy is not an alternative.
• Majority of patients can be cured with normalisation of pulmonary pressure following surgery with improvement in symptoms and prognosis, with a > 90% 5 year survival.
• Patients unsuitable for pulmonary endarterectomy surgery and patients who still have residual PH following pulmonary endarterectomy surgery might be considered for treatment with the drugs described above.

Endothelin receptor antagonists

• A systematic review concluded (1)
  • endothelin receptor antagonists probably increase exercise capacity, improve World Health Organization functional class (a measurement
    of how severe a person's pulmonary hypertension symptoms are), and may improve death rates and symptoms in people with PAH;
    however they may also increase the risk of liver damage, although this was rare.

In selected patients who have class 4 symptoms despite optimal medical therapy, bilateral lung or heart lung transplantation may be considered. The 5 year survival following transplantation is approximately 50-60%.

Notes:

• A meta-analysis showed evidence an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension (2).
  • With respect to the effects of the different classes of drugs (prostanoids, thromboxane synthase inhibitors, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors), no statistically significant between-group heterogeneity emerged in subgroup analyses in total mortality or between the subgroups testing each of the treatments.
    
• The clinical classification of pulmonary hypertension is helpful in understanding the different aetiology and determining treatment (3):
  • Group 1 Pulmonary arterial hypertension (PAH)
    • idiopathic PAH
    • PAH associated with connective tissue disease: predominantly seen with scleroderma
  • Group 2 Left heart disease
    • PH associated with left heart dysfunction, systolic, diastolic or valve disease
  • Group 3 Lung disease
    • PH in patients with COPD or interstitial lung disease
  • Group 4 Chronic thromboembolic pulmonary hypertension
  • Group 5 Unclear and multifactorial mechanisms
    • Rare diseases.
      
• World Health Organization classification functional status in primary pulmonary hypertension:
  • class I - no limitation on physical activity functional
  • class II - slight limitation functional class
  • III - pronounced limitation functional
  • class IV - inability to carry out any physical activity without symptoms.

References:

• (1) Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database Syst Rev. 2021 Mar 26;3(3):CD004434. doi: 10.1002/14651858.CD004434.pub6. (Accessed on 15 Aug 2022).
• (2) Galie N et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension Eur Heart J. 2009 Feb;30(4):394-403.
• (3) British Heart Foundation (June 2022). Lungs under pressure: Impact of BHF support for pulmonary hypertension research. Available at https://www.bhf.org.uk/what-we-do/our-research/impact-of-pulmonary-hypertension (Accessed 15 Aug 2022).